Post-transcriptional Modifications Contribute to the Upregulation of Cyclin D2 in Multiple Myeloma

Misiewicz-Krzemińska, Irena; Sarasquete, María Eugenia; Vicente-Dueñas, Carolina; Krzemiński, Patryk; Wiktorska, Katarzyna; Corchete, Luis A.; Quwaider, Dalia; Rojas, Elizabeta A.; Corral, Rocío; Martín, Ana A.; Escalante, Fernando; Bárez, Abelardo; Garcı́a, Juan Luis; Sánchez-Garcı́a, Isidro; Miguel, Jesús F. San; Gutiérrez, Norma C.

doi:10.1158/1078-0432.ccr-14-2796

Cited by 23 publications

(25 citation statements)

References 38 publications

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“…Both genes have been implicated in the tumorigenesis of many human cancers. [41][42][43][44] In conclusion, our study demonstrates that a significant number of…”

Section: Discussionsupporting

confidence: 58%

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ETV transcriptional upregulation is more reliable than RNA sequencing algorithms and FISH in diagnosing round cell sarcomas with CIC gene rearrangements

Kao

Sung

Chen

et al. 2017

Genes Chromosomes & Cancer

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CIC rearrangements have been reported in two-thirds of EWSR1-negative small blue round cell tumors (SBRCTs). However, a number of SBRCTs remain unclassified despite exhaustive analysis. Fourteen SBRCTs lacking driver genetic events by RNA sequencing (RNAseq) analysis were collected. Unsupervised hierarchical clustering was performed using samples from our RNAseq database, including 13 SBRCTs with non-CIC genetic abnormalities and 2 CIC-rearranged angiosarcomas among others. Remarkably, all 14 study cases showed high mRNA levels of ETV1/4/5, and by unsupervised clustering most grouped into a distinct cluster, separate from other tumors. Based on these results indicating a close relationship with CIC-rearranged tumors, we manually inspected CIC reads in RNAseq data. FISH for CIC and DUX4 abnormalities and immunohistochemical stains for ETV4 were also performed. In the control group, only 2 CIC-rearranged angiosarcomas had high ETV1/4/5 expression. Upon manual inspection of CIC traces, 7 of 14 cases showed CIC-DUX4 fusion reads, 2 cases had DUX4-CIC reads, while the remaining 5 were negative. FISH showed CIC break-apart in 7 cases, including 5 cases lacking CIC-DUX4 or DUX4-CIC fusion reads on RNAseq manual inspection. However, no CIC abnormalities were detected by FISH in 6 cases with CIC-DUX4 or DUX4-CIC reads. ETV4 immunoreactivity was positive in 7 of 11 cases. Our results highlight the underperformance of FISH and RNAseq methods in diagnosing SBRCTs with CIC gene abnormalities. The downstream ETV1/4/5 transcriptional up-regulation appears highly sensitive and specific and can be used as a reliable molecular signature and diagnostic method for CIC fusion positive SBRCTs.

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“…Both genes have been implicated in the tumorigenesis of many human cancers. [41][42][43][44] In conclusion, our study demonstrates that a significant number of…”

Section: Discussionsupporting

confidence: 58%

“…NOTCH1 signaling pathway plays an important role in embryonic development, whereas CCND2 encodes cyclin D2 that controls cell cycle progression from G1 to S phase. Both genes have been implicated in the tumorigenesis of many human cancers …”

Section: Discussionmentioning

confidence: 99%

ETV transcriptional upregulation is more reliable than RNA sequencing algorithms and FISH in diagnosing round cell sarcomas with CIC gene rearrangements

Kao

Sung

Chen

et al. 2017

Genes Chromosomes & Cancer

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“…Normal_MM, the healthy control peripheral blood samples for multiple myeloma; MM_MM, the multiple myeloma peripheral blood samples; Normal_PC, the healthy control peripheral blood samples for prostate cancer; PC_PC, the prostate cancer peripheral blood samples; CRISP3, cysteine-rich secreted protein 3. to be over expressed in cervical intraepithelial neoplasia (23). CCND2 is a cellular cyclin that has been previously demonstrated to be upregulated in MM (24). In the present study, gene expression of CRISP3, A1BG, CCND2 and Oct2 were additionally validated in whole peripheral blood samples from healthy controls and patients with MM by RT-qPCR (Fig.…”

Section: Transcriptional Changes Of Genes Validated By Rt-qpcrsupporting

confidence: 51%

Inï¿½silico analysis identifies CRISP3 as a potential peripheral blood biomarker for multiple myeloma: From data modeling to validation with RT-PCR

et al. 2018

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Abstract. Octamer-binding protein 2 (Oct2) binds to the ATGCAAAT octamer on the IgH enhancer and stimulates IgH expression in human multiple myeloma (MM). Cysteine-rich secreted protein 3 (CRISP3) possesses the ATGCAAAT sequence and thus is activated by Oct2 in mouse B cells, suggesting that CRISP3 may be activated in and be a potential biomarker for MM. The present study involved a meta-analysis of the gene expression profiling data of human MM peripheral blood. Significantly expressed genes were analyzed on merged super array microarray data and selected sample data with significantly expressed genes were additionally analyzed by principal component analysis and Bayesian probit regression. CRISP3, Oct2, Apha-1B-glycoprotein (A1GB) and Cyclin D2 (CCND2) were validated in clinical MM peripheral blood samples using reverse transcription quantitative polymerase chain reaction. In the gene expression profiling data, CRISP3 was significantly upregulated and had certain proportions on the discriminated principal component of significantly expressed gene sample data. RT-qPCR analysis revealed CRISP3 was significantly upregulated in MM. Therefore, CRISP3 is a potential peripheral blood biomarker for MM.

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“…Oncogene transcripts that undergo 3 UTR truncation often exhibit enhanced oncogenic properties [77,78].…”

Section: Utr Shortening Transforms the Mirna Regulatory Landscapementioning

confidence: 99%

The Butterfly Effect of RNA Alterations on Transcriptomic Equilibrium

Desi

Tay

2019

Cells

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Post-transcriptional regulation plays a key role in modulating gene expression, and the perturbation of transcriptomic equilibrium has been shown to drive the development of multiple diseases including cancer. Recent studies have revealed the existence of multiple post-transcriptional processes that coordinatively regulate the expression and function of each RNA transcript. In this review, we summarize the latest research describing various mechanisms by which small alterations in RNA processing or function can potentially reshape the transcriptomic landscape, and the impact that this may have on cancer development.

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Post-transcriptional Modifications Contribute to the Upregulation of Cyclin D2 in Multiple Myeloma

Cited by 23 publications

References 38 publications

ETV transcriptional upregulation is more reliable than RNA sequencing algorithms and FISH in diagnosing round cell sarcomas with CIC gene rearrangements

ETV transcriptional upregulation is more reliable than RNA sequencing algorithms and FISH in diagnosing round cell sarcomas with CIC gene rearrangements

Inï¿½silico analysis identifies CRISP3 as a potential peripheral blood biomarker for multiple myeloma: From data modeling to validation with RT-PCR

The Butterfly Effect of RNA Alterations on Transcriptomic Equilibrium

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